The mitochondrion serves a central role in cellular iron metabolism. It is the, site of the final step of heme biosyntheses, addition of Fe2+ to protoporphyrin, and contains a large amount of non-heme iron in the iron sulfur centers of the electron transport chain. In spite of its importance for normal mitochondrial function, very few human disorders have been described which result from abnormalities in mitochondrial iron homeostasis.
Sideroblastic anemias are a heterogenous group of disorders, characterized by hypochromic microcytic erythrocytes and iron accumulation in the mitochondria of bone marrow erythrocyte precursors. The disorder can be both acquired or inherited, and the mode of transmission may be mitochondrial, autosomal or X-linked.
The ATP-binding cassette (ABC) superfamily of transporters contains conserved in evolution proteins involved in energy-decedent transport of a wide variety of substrates across cell membranes, including those of organelles such as the mitochondria, peroxisomes and endoplasmic reticulum. Many ABC genes have been implicated in different inherited diseases, including cystic fibrosis, adrenoleukodystrophy and a number of retinal dystrophies.
A recent study by Savary et al., (Genomics (1997) 41:275-278), reports genomic mapping of the ATP binding cassette-7 (ABC7) in mouse and humans. Savary et al also provides a partial sequence related to human ABC7 and its alignment with the yeast and murine ABC7 protein to identify conserved sequences. In this study the gene encoding human ABC7 was mapped to the Xq12-q13 region of the human genome. Additionally, a study by Shimada et al., (J. Hum. Genet. 43(2), 115-122 (1998)) describes the cloning of hABC7 having GenBank assession no. AB005289.
The mitochondrial ABC protein (Atm1p), encoded by the ATM1 gene has been, described in yeast and found to be essential for the cell growth and maintenance of mitochondrial DNA. Yeast strains, deficient for the ATM1 gene, have been shown to accumulate high levels of iron in mitochondria.